1. Field of the Invention
The present invention relates to a process for producing threo-3-(3,4-dihydroxyphenyl)serine.
2. Description of the Related Art
Threo-3-(3,4-dihydroxyphenyl)serine III! (hereinafter described as threo DOPS) is pharmacologically active towards the circulatory system and the central nervous system, and, when administered to a patient, has efficacy against certain ailments, such as peripheral orthostatic hypotension and Parkinson disease, among others, and has efficacy as an antidepressant. This compound has been produced, for example, by using a derivative M of N-butoxycarbonyl DOPA obtained from N-acyl-3,4-dihydroxyphenylalanine (hereinafter referred to as DOPA) via three or four steps as described in Japanese Patent Kokai (Laid-Open) No. 1-228946. ##STR3##
In this multi-step process, the oxazolidone intermediate having an acetoxymethyl group at the 4-position, compound VII!, is produced via following three reaction steps:
(1) reducing an alkoxycarbonyl moiety of the derivative V! of N-butoxycarbonyl DOPA to form an alcohol; PA1 (2) acetylating the alcohol to obtain an acetoxy-form VI!; and PA1 (3) reacting the acetoxy-form VI! with potassium persulfate in the presence of a copper catalyst to obtain the oxazolidone VII! intermediate. PA1 (4) the oxazolidone ring is opened; PA1 (5) the alcohol moiety derived from an acetoxy group is oxidized and converted into a carboxyl group; and then PA1 (6) protecting groups and halogen(s) are removed to obtain threo DOPS III! as a final product.
Thereafter, at least three further reaction steps are required before obtaining the desired threo-DOPS III!:
Disadvantageously, however, this process requires at least six steps. This six-step operation is complicated and the yield of the final product, based on DOPA A! as the starting material, is low.
It would be a significant advance to provide a more synthetically facile process for making threo DOPS III!.
A synthetically facile process which produces the desired threo DOPS III! in higher yields with good selectivity would be particularly advantageous.
Such a process which is capable of being industrially practiced is particularly desirable.
Those skilled in the art have been seeking such processes.